Figure 6.
Doxycycline sensitizes to MAPKi in preclinical models and in one melanoma patient. (A) Tumor volume of cohorts of Mel-007 BRAFV600 PDX mice (resistant to MAPKi) treated with DT (n = 3) or DTT (n = 4). Data are mean ± SEM of different biological replicates. ****, P < 0.0001 by two-way ANOVA. (B) Histology and immunohistochemistry of the bile duct biopsy confirming the presence of melanoma metastasis in one melanoma patient. Scale bar = 25 µm. (C) Case presentation of a patient with MAPK inhibitory therapy and sporadic exposure to doxycycline. Baseline PET-CT revealed liver (lower left, right-hand image) and gallbladder metastasis (lower left, left-hand image). First response assessment showed disappearance of the liver metastasis but a persistent gallbladder lesion (4 mo of treatment). Adding doxycycline to MAPK inhibitory therapy showed shrinkage after two more cycles of treatment (CT scan not depicted), which was subsequently confirmed by PET-CT after 8 mo on treatment, revealing a complete metabolic response. After >36 mo, the patient is still responding to the treatment.